Moderna and Merck announced Wednesday that their experimental personalized mRNA cancer vaccine, administered alongside Merck’s immunotherapy Keytruda, met its primary goal of significantly extending recurrence-free survival in a Phase 3 trial enrolling more than 1,100 melanoma patients whose tumors had been surgically removed, sending Moderna shares up nearly 150 percent.
Merck shares climbed more than 10 percent. The disparity reflected the companies’ relative market sizes entering Wednesday: Merck’s market cap stood near $333 billion, while Moderna’s sat around $25 billion.
The combination regimen also reduced the risk of cancer spreading to distant parts of the body compared with Keytruda alone, the standard of care for melanoma. Both the recurrence-free survival and distant metastasis-free survival extensions were statistically significant and clinically meaningful. The companies did not elaborate.
How the vaccine works
The vaccine, known as intismeran or mRNA-4157, uses synthetic mRNA that carries the genetic coding for up to 34 mutations unique to a patient’s own cancer cells. The production process involves comparing the genetic sequences of a patient’s cancer cells to those of healthy cells and selecting cancer-specific mutations that could help the immune system distinguish between cancerous and healthy tissue. The vaccine trains the immune system to recognize and kill those unique cancer markers, and that response is paired with Keytruda, which helps the body attack the cancer more effectively.
Every tumor has a unique set of mutations, even among patients with the same type of cancer, according to Dr. Jane Healy, Merck’s head of oncology early development. The personalized approach targets the specific mutations in each patient’s tumor rather than using a one-size-fits-all method. The results validate a treatment approach that Merck and Moderna have been developing for decades, she added.
Trial design and next steps
The Phase 3 trial enrolled 1,137 patients with stage IIB through IV melanoma that had been surgically removed before treatment. Patients were randomized two-to-one to receive either the combination of the tailored mRNA vaccine with Keytruda or Keytruda alone, with both patient groups treated for about a year in the placebo-controlled, double-blind study.
The Phase 3 study will continue to assess other outcomes, including overall survival. The drugmakers plan to present the data at an upcoming international medical meeting, but it remains unclear when they intend to submit applications for approval in the United States. Dr. Dean Li, president of Merck Research Laboratories, said the companies will likely begin talking to regulatory agencies about the treatment and its safety in the next few months.
The initial results build on Phase 2 data presented at a cancer research conference in June, which showed a 49 percent reduction in the risk of recurrence or death and a 59 percent reduction in the risk of distant metastasis or death. Side effects in the Phase 3 trial were similar to those of other vaccines people typically receive for other diseases, and the treatment was well tolerated by patients, Healy noted.
Moderna CEO Stephane Bancel called it “a big moment for medicine, a big moment for patients” in an interview on CNBC’s “Squawk Box.” Healy said it was “very exciting” that the therapy led to a “clinically meaningful improvement” over Keytruda and was well tolerated. She described the patient experience in an interview, noting that melanoma patients are “stuck having to deal with the new gravity of that diagnosis and then undergo uncomfortable treatments like surgery, and after that, they’re worried about their cancer coming back.”
She said the results are “very meaningful for patients with this disease and really the potential of what it can mean for other patients for cancer in future trials with this particular new class of therapy.” The announcement, though scant on details, represents a first late-stage success for both mRNA vaccines and individualized cancer-targeting medicines. If the success holds, it would realize the high aspirations for both treatment types in cancer therapy.
Melanoma accounts for only about one percent of skin cancers but causes the large majority of skin cancer deaths. Most recurrences develop in the first two to three years after initial treatment and removal.
Analysts had flagged the Phase 3 results as a make-or-break event for Moderna’s stock, according to a June note from Leerink Partners analyst Mani Foroohar. Before Wednesday’s stock move, the company’s valuation already reflected expectations that the personalized cancer vaccine could eventually work across multiple types of cancers. Merck and Moderna are studying the vaccine in several trials across other tumors, including non-small cell lung cancer, bladder cancer, and renal cell carcinoma.